Objective: To investigate the relationship between serum interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α) and the severity of mycoplasma pneumonia in children. Methods: A total of 150 children with mycoplasma pneumonia admitted to General Hospital of Anhui Wanbei Coal Power Group from January 2018 to December 2020 were included. The children were divided into a mild group (83 cases) and a severe group (67 cases) according to whether they had severe mycoplasma pneumonia. The children were also divided into an asthmatic group (127 cases) and a non-asthmatic group (23 cases) according to whether they had asthmatic pneumonia. Gender, age, course of disease, serum sodium, serum potassium, C-reactive protein (CRP), TNF-α and IL-6 levels before and after the treatment were recorded to analyze the relationship between TNF-α or IL-6 and the severity of disease in children. Results: There were no significant differences in gender, age, hyponatremia, and hypokalemia between the two groups (P>0.05). The course of disease was longer and CRP was higher in the severe group (P<0.05). After the treatment, the expression levels of TNF-α and IL-6 were significantly decreased. Before and after the treatment, the levels of TNF-α and IL-6 in the severe group were higher than those in the mild group (P<0.05). The incidence of asthmatic symptoms was higher in the severe group, and the levels of TNF-α and IL-6 in the children with asthmatic were higher than those without asthmatic (P<0.05). Conclusion: Serum levels of TNF-α and IL-6 differ between children with mild and severe mycoplasma pneumonia. Serum levels of TNF-α and IL-6 can be used as one of the guiding basis for the judgment of the disease in children with mycoplasma pneumonia.